Neural crest cells migrate extensively during development. This invasive behavior is spatially and temporally precise, and the cells eventually form such diverse derivatives as: pigment cells, sensory and autonomic ganglia, teeth and the cranial connective tissues. Changes in distribution and composition of the extracellular matrix on the crest cells may be related to the onset of neural crest cell movement and to the control of the pattern, pathway, and direction of their migration. I plan to investigate the role of the extracellular matrix in the control of 1) the initiation of migration from the neural tube and 2) the determination of specific migratory pathways. I will correlate these events with changes in the extracellular matrix (ECM) in normal mice. In addition I will examine mouse mutants in which neural cret morphogenesis is perturbed and in which the extracellular matrix has been implicated. These studies should provide more direct evidence than has been possible before concerning the role of the extracellular matrix in morphogenesis. Finally, tissue culture studies should reveal the mechanisms by which the extracellular matrix exerts its control over neural crest cell movement and differentiation.